Nanopatterns on silica scales of Mallomonas (Chrysophyceae, Stramenopiles): Unraveling UV resistance potential and diverse response to UVA and UVB radiation.

Mallomonas thrive primarily in freshwaters and dominate plankton communities, especially in oligotrophic waters. The cells have a siliceous cell covering of regularly arranged scales. Despite their ecological importance, the intricate structure and evolutionary significance of their silica scales are still unexplored. We investigated the nanopatterns on the scales and hypothesized that they may play a role in UV shielding. UVA and UVB exposure experiments were performed with 20 Mallomonas species, categorized into four groups based on the nanopattern of the scales (plain-scaled, meshed, striated, and papilliferous group); a fifth group consisted of the species that have extremely thick, robust scales regardless of the nanopattern. We revealed that thick scales were associated with enhanced UVB resistance, suggesting a protective role. No significant differences in UVA response were observed among the groups, except for the meshed group, which showed lower resistance, likely due to the less regular pattern on the shield. In conclusion, the scale case, composed of sufficiently silicified scales, provides effective UV protection in freshwater environments, regardless of the particular nanopattern. In increased UVB radiation, the thickness of the scales plays role. Contrary to expectations, cell size and phylogeny do not strongly predict UV resistance. The study highlights the diverse UV responses of Mallomonas, but further studies are needed to understand the role of scales/nanopatterns in the ecological adaptations of the species.

A Comprehensive Analysis of Skin Cancer Concerns and Protective Practices in Manitoba, Canada, Highlights Lack of Skin Cancer Awareness and Predominance of High-Risk Sun Exposure Behaviors.

The rapidly increasing skin cancer rates in Canada are alarming, with current data estimating that 1/3 of Canadians will be affected in their lifetime. Thus, deeper understanding of high-risk sun exposure behaviors is needed to help counter this trend. Only limited action has been taken by federal/provincial governments to reduce skin cancer incidence. A cross-sectional survey study was conducted in Manitoba, with frequency counts, means, and percentages used to encapsulate responses. Age- and gender-adjusted odds ratios were calculated using logistic regression analyses. Our study identified worrying inadequacies in sun protective behaviors and attitudes, with the threat of such high-risk behaviors amplified by a lack of skin cancer awareness. Alarming elements were noted in participants' sun exposure history (>65% reported a history of sunburns, >50% previously used a tanning bed, and >75% recently tanned for pleasure), beliefs and attitudes (>50% believe that they look better/healthier with a tan, and >40% believe that having a base tan is protective against further sun damage), and sun protection efforts (sun protective clothing was used <60% of the time, sunscreen was used by <50%, and there was a lack of knowledge about sunscreen characteristics in ~30% of respondents), in addition to significant differences being established between demographic subgroups (based on gender, age, skin phototype, income, and education attained). This study provides worrisome insight onto the grim landscape of sun protective behaviors and attitudes in Manitoba, which will inevitably translate into higher skin cancer rates and should serve as a call to action to promote targeted public health messaging in this jurisdiction and beyond.

Effect of UV exposure and natural aging on the in vitro PAHs bioaccessibility associated with tire wear particles in soil.

Tire wear particles (TWP), as an emerging type of microplastics, are a significant source of contaminants in roadside soils due to their high concentration of pollutants, including polycyclic aromatic hydrocarbons (PAHs). This study explored the impact of ultraviolet (UV) exposure and natural aging on the in vitro bioaccessibility of PAHs associated with TWP in soil on a China-wide scale. Our findings suggested that UV exposure amplified the negative charge of TWP by 75 % and increased the hydrophobic groups on the particle surface. The bioaccessibility of 3- and 4-ring PAHs in TWP was significantly (p < 0.05) heightened by UV exposure. After 20 types of soils containing 2 % UV-exposed TWP underwent natural aging, the bioaccessibility of PAHs saw a significant decrease (p < 0.05) to 16-48 %, compared to 28-96 % in the unaged group. Soil pH and electrical conductivity (EC) were the two primary soil properties positively influencing the reduction of in vitro PAHs concentration and PAHs bioaccessibility. According to the prediction results, soils in southern China presented the highest potential region for the release of bioaccessible PAHs from TWP, highlighting the regional specificity of environmental impact. Our study provides valuable insights into the biological impact of PAHs associated with TWP on a regional scale, and offers scientific evidence for targeted soil risk management strategies.

Data Processing for Predicting DNA Damaging Properties of Complex UV Sources.

A growing number of experimental evidence emphasizes that photobiological phenomena are not always the sum of the effect of individual wavelengths present in the emission spectrum of light sources. Unfortunately, tools are missing to identify such non-additive effects and predict effects of various exposure conditions. In the present work, we addressed these points for the formation of pyrimidine dimers in DNA upon co-exposure to UVC, UVB and UVA radiation. We first applied a combination index approach to determine whether mixtures of theses UV ranges exhibited additive, inhibitory or synergistic effects on the formation of cyclobutane pyrimidine dimers, (6-4) photoproducts and Dewar valence isomers. A predictive approach based on an experimental design strategy was then used to quantify the contribution of each wavelength range to the formation of DNA photoproducts. The obtained models allowed us to accurately predict the level of pyrimidine dimers in DNA irradiated under different conditions. The data were found to be more accurate than those obtained with the simple additive approach underlying the use of action spectra. Experimental design thus appears as an attractive concept that could be widely applied in photobiology even for cellular experiments.

Study on the Influence of UV Light on Selective Antibacterial Activity of Silver Nanoparticle Synthesized Utilizing Protein/Polypeptide-Rich Aqueous Extract from The Common Walkingstick, Diapheromera femorata.

Common walkingstick (Diapheromera femorata) aqueous extract (CWSAE) can induce the synthesis of useful bionanomaterials. CWSAE is rich in water-soluble organic compounds such as proteins and polypeptides that function as reducing/stabilizing agents for nanoparticle formation from Ag+ ion precursors. The synthesized AgNPs exhibited a moderately uniform size, with the majority falling within the range of 20-80 nm. These AgNPs were UV-treated and tested as antibacterial agents to inhibit the growth of four pathogenic bacteria (Burkholderia cenocepacia K-56, Klebsiella pneumoniae ST258, Pseudomonas aeruginosa PAO1, and Staphylococcus aureus USA300), as well as one common bacterium (Escherichia coli BW25113). The disk diffusion test demonstrated that the UV-treated AgNPs significantly and selectively inhibited the growth of Staphylococcus aureus USA300 and P. aeruginosa, while showing a small effect on the other two species. This suggests the potential application of green-chemically synthesized AgNPs as selective antibacterial agents. Furthermore, we studied the effects of short-term (1-2 min) and long-term (5-30 min) UV treatment on the selective cytotoxicity of the AgNPs and found that the cytotoxicity of the AgNPs could depend on the duration of UV exposure against certain bacteria.

Genotoxicity of ultraviolet light and sunlight in the bacterium Caulobacter crescentus: Wavelength-dependence.

The ultraviolet (UV) component of sunlight can damage DNA. Although most solar UV is absorbed by the ozone layer, wavelengths > 300 nm (UVA and UVB bands) can reach the Earth's surface. It is essential to understand the genotoxic effects of UV light, particularly in natural environments. Caulobacter crescentus, a bacterium widely employed as a model for cell cycle studies, was selected for this study. Strains proficient and deficient in DNA repair (uvrA-) were used to concurrently investigate three genotoxic endpoints: cytotoxicity, SOS induction, and gene mutation, using colony-formation, the SOS chromotest, and RifR mutagenesis, respectively. Our findings underscore the distinct impacts of individual UV bands and the full spectrum of sunlight itself in C. crescentus. UVC light was highly genotoxic, especially for the repair-deficient strain. A UVB dose equivalent to 20 min sunlight exposure also affected the cells. UVA exposure caused a significant response only at high doses, likely due to activation of photorepair. Exposure to solar irradiation resulted in reduced levels of SOS induction, possibly due to decreased cell survival. However, mutagenicity is increased, particularly in uvrA- deficient cells.

Assessing Skin Cancer Risk Factors, Sun Safety Behaviors and Melanoma Concern in Atlantic Canada: A Comprehensive Survey Study.

BACKGROUND: The incidence of cutaneous melanoma (CM) is increasing at an alarming rate in Canada and elsewhere around the world. Significant regional differences in CM incidence have been identified in Atlantic provinces. The goal of this study is to compare ultraviolet exposure, sun protective behaviours, level of worry and baseline CM knowledge in provinces with a high versus low incidence of CM as well, as between various demographic groups. METHODS: A cross-sectional survey study was conducted in Atlantic provinces between July 2020 and August 2022. All participants aged ≥ 16 years with a completed survey were eligible. Survey responses were summarized using frequency counts, percentages, and means. Two-sided Z-tests for equality of proportions and logistic regression models were used to compare the survey results between geographic and demographic groups. RESULTS: In total, 7861 participants were included (28.0% men; mean age 61.3 years; response rate 28%). Our results (gender- and age-adjusted odds ratio, 95% confidence interval) show that high-incidence provinces for CM (Prince Edward Island and Nova Scotia) had significantly more sunburns (OR 2.00, 1.72-2.31), total sun exposure (OR 2.05, 1.68-2.50), recreational sun exposure (OR 1.95, 1.61-2.35) and tans (OR 1.77, 1.53-2.05) than individuals in low-incidence provinces (Newfoundland and Labrador). However, individuals in high-incidence provinces displayed more protective behaviors: there were less tanning bed users (OR 0.82, 0.71-0.95), they checked their skin more frequently for new moles (OR 1.26, 1.06-1.51) and practiced more sun protection overall. Additional analyses are presented based on education, income, sexual orientation and gender. DISCUSSION: These findings suggest that future efforts aimed at reducing the CM burden in Atlantic Canada should be tailored for target geographic and/or demographic groups. LIMITATIONS: the study participants are not representative of the population in Atlantic Canada due to recruitment strategies.

A Study on the Candidate Gene Association and Interaction with Measures of UV Exposure in Pseudoexfoliation Patients from India.

PURPOSE: Environmental and genetic factors are associated with development of Pseudoexfoliation syndrome (XFS). Here we intended to elucidate the association of candidate genes in relevance to UV exposure in these patients. METHODS: This is a case-control study of 309 subjects (N = 219 controls and 90 XFS cases) from India. PCR based direct sequencing was performed for candidate genes (LOXL1, POMP and TMEM136) followed by genotype and haplotype analysis. The promoter methylation status was assessed by Methylation specific PCR based direct sequencing of genomic DNA for all samples. The methylation status was compared with that of primary fibroblasts cultures established from patient's Tenon's tissue samples in subset of these patients. RESULTS: SNPs rs3825942, rs41435250, rs8818 (LOXL1) and rs3737528 (POMP) showed significant association with XFS. LOXL1 gene haplotype GAGC (rs1048661- rs3825942- rs41435250-rs8818) was associated with lower risk for XFS with a p value 4.1961 × 10-6 (OR =0; 95%CI, 0.000-0.003). POMP gene haplotypes for intronic SNPs (rs1340815- rs3737528- rs913797) TCC and TTC were associated with increased risk for the disease (OR > 1.0). Significant correlation for SNPs rs3825942 of LOXL1 (ρ= -0.132) and rs3737528 of POMP (ρ = 0.12) was observed with measure of lifetime UV exposure (CUVAF value). Reduced LOXL1 gene expression was observed in cultured tenon fibroblasts from the patients that correlated with differential methylation of the Sp-1 binding sites at -253, -243bp upstream to the transcription start site of LOXL1 promoter region. CONCLUSION: Our results suggest a possible interaction for LOXL1 gene haplotype (GAGC) with the measure of ocular UV exposure in pseudoexfoliation syndrome.

Benefits and Risks of Sun Exposure to Maintain Adequate Vitamin D Levels.

Vitamin D is a hormone that can be generated in the skin upon ultraviolet light exposure or ingested through supplementation. Vitamin D deficiency may have numerous deleterious effects on health. Sun avoidance strategies should be avoided due to the unwanted health risks associated with hypovitaminosis D. We present an objective investigation of the benefits and risks of using sun exposure to increase vitamin D levels and how it impacts human health. A review of the literature was conducted using Embase and PubMed to examine the relationship between UV exposure, vitamin D levels, health benefits, and risks. UV exposure is the primary method of boosting serum vitamin D levels, which accounts for numerous health benefits. Higher levels of vitamin D are associated with protection against cancer development, including melanoma. Latitude, season, skin color, and sun protection determine UV absorption and vitamin D production. Public health sun protection guidelines decrease the incidence of skin cancer, but sun avoidance can cause hypovitaminosis D. Serum vitamin D levels less than 16 nmol/L increase morbidity through increased non-cutaneous disease. Sun protection strategies should still be implemented to reduce skin cancer, and sunscreen only minimally lowers vitamin D production. Vitamin D deficiency can increase chronic diseases and cancer, while adequate vitamin D levels can help prevent them. UV exposure and vitamin D production are dependent on many factors. Increasing UV exposure without causing sunburn maximizes vitamin D production.

New Chemically Amplified Positive Photoresist with Phenolic Resin Modified by GMA and BOC Protection.

In this paper, a chemically amplified (CA) i-line photoresist system is described including a phenolic resin modified with glycidyl methacrylate (GMA) addition and protected with di-tert-butyl dicarbonate (BOC group), here called JB resin. JB resin with different degrees of BOC protection was synthesized and characterized with ultraviolet spectrophotometry, Fourier transform infrared spectroscopy and gel permeation chromatography. These resins were also evaluated in CA resists by formulating the JB resin with a photoacid generator (PAG) and tested at 405 nm and 365 nm exposure wavelengths. The BOC protection ratio at approximately 25 mol% of the Novolak phenol group showed the best performance. The resist showed high sensitivity (approximately 190 mJ/cm2), high resolution and good alkali developer resistance with reliable repeatability, indicating the great practical potential of this JB resist system.

Physicochemical Properties of UV-Irradiated, Biaxially Oriented PLA Tubular Scaffolds.

PLA and its blends are the most extensively used materials for various biomedical applications such as scaffolds, implants, and other medical devices. The most extensively used method for tubular scaffold fabrication is by using the extrusion process. However, PLA scaffolds show limitations such as low mechanical strength as compared to metallic scaffolds and inferior bioactivities, limiting their clinical application. Thus, in order to improve the mechanical properties of tubular scaffolds, they were biaxially expanded, wherein the bioactivity can be improved by surface modifications using UV treatment. However, detailed studies are needed to study the effect of UV irradiation on the surface properties of biaxially expanded scaffolds. In this work, tubular scaffolds were fabricated using a novel single-step biaxial expansion process, and the surface properties of the tubular scaffolds after different durations of UV irradiation were evaluated. The results show that changes in the surface wettability of scaffolds were observed after 2 min of UV exposure, and wettability increased with the increased duration of UV exposure. FTIR and XPS results were in conjunction and showed the formation of oxygen-rich functional groups with the increased UV irradiation of the surface. AFM showed increased surface roughness with the increase in UV duration. However, it was observed that scaffold crystallinity first increased and then decreased with the UV exposure. This study provides a new and detailed insight into the surface modification of the PLA scaffolds using UV exposure.

Safe-Shields: Basal and Anti-UV Protection of Human Keratinocytes by Redox-Active Cerium Oxide Nanoparticles Prevents UVB-Induced Mutagenesis.

Cerium oxide nanoparticles (nanoceria), biocompatible multifunctional nanozymes exerting unique biomimetic activities, mimic superoxide-dismutase and catalase through a self-regenerating, energy-free redox cycle driven by Ce3+/4+ valence switch. Additional redox-independent UV-filter properties render nanoceria ideal multitask solar screens, shielding from UV exposure, simultaneously protecting tissues from UV-oxidative damage. Here, we report that nanoceria favour basal proliferation of primary normal keratinocytes, and protects them from UVB-induced DNA damage, mutagenesis, and apoptosis, minimizing cell loss and accelerating recovery with flawless cells. Similar cell-protective effects were found on irradiated noncancerous, but immortalized, p53-null HaCaT keratinocytes, with the notable exception that here, nanoceria do not accelerate basal HaCaT proliferation. Notably, nanoceria protect HaCaT from oxidative stress induced by irradiated titanium dioxide nanoparticles, a major active principle of commercial UV-shielding lotions, thus neutralizing their most critical side effects. The intriguing combination of nanoceria multiple beneficial properties opens the way for smart and safer containment measures of UV-induced skin damage and carcinogenesis.

Sun Protection in German Outdoor Workers: Differences by Sex and Job-Related Characteristics.

BACKGROUND: Ultraviolet (UV) exposure during outdoor work increases the risk of developing skin cancer. Therefore, the uptake of recommended sun protection behaviors is important to prevent UV-related skin damage in the population of outdoor workers. To develop targeted prevention campaigns, information on the use of sun protection behaviors in different industries is needed. METHODS: A total of 486 outdoor workers were surveyed on the use of several sun protection measures as part of the 7th wave of the National Cancer Aid Monitoring. Furthermore, details on job-related characteristics, sociodemographics, and skin type were assessed. Descriptive analyses stratified by sex were conducted. RESULTS: In general, use of sun protection was insufficient (e.g. 38.4% used sunscreen on the face). Sun protection behavior differed between female and male outdoor workers with females being more likely to use sunscreen and males being more likely to wear sun protective clothes and headgear. For male outdoor workers, we revealed several associations with job-related characteristics. For instance, those who were employed full time were more likely to wear sun protective clothes (e.g. shoulder-covering shirt: 87.1% versus 50.0%, P < 0.001). DISCUSSION: We identified deficits in sun protection behavior in outdoor workers and differences by sex- and job-related characteristics. These differences offer starting points for targeted prevention measures. In addition, the findings may inspire qualitative research.

Effects of UV Stress in Promoting Antioxidant Activities in Fungal Species Тrametes versicolor (L.) Lloyd and Flammulina velutipes (Curtis) Singer.

Trametes versicolor and Flammulina velutipes, after submerged cultivation, with intermittent exposure to ultraviolet light (UV), were studied for Total Phenolic content (TP) and Total Proteins (TPR) contents and antioxidant properties against free radicals. The TP and TPR were determined by a spectrophotometric method and Lowry's assay, respectively. Liquid chromatography with mass spectrometry (LC-MS/MS) was used to quantify polyphenols. Different in vitro assays determined the antioxidant activities of the extracts. Mycelia extract from F. velutipes after 14 days and filtrate from T. versicolor after 21 days of incubation gave the highest TP 59.60 ± 0.14 and 50.03 ± 0.66 mg GAE/g d.w., respectively. Mycelia extract from T. versicolor after 28 days of incubation had the highest TPR (183.53 ± 2.84 mg BSAE/g d.w.). The LC-MS/MS analysis indicated that p-hydroxybenzoic and protocatechuic acids are the most abundant. Trametes versicolor filtrate after 14 days and F. velutipes filtrate after 21 days (71.29 ± 0.54% and 73.5 ± 1.81, respectively) had the highest scavenging activity in SOA. Correlation analysis indicated that all extracts' antioxidant (AO) potential strongly correlated with TP (R2 = 0.83-1.0). The data confirmed that stress factors such as UV exposure could stimulate the production of secondary metabolites and natural AOs, especially phenolic acids in test fungi.

Implication of E3 ligase RAD18 in UV-induced mutagenesis in human induced pluripotent stem cells and neuronal progenitor cells.

Pluripotent stem cells (PSCs) have the potential to differentiate to any of the other organs. The genome DNA integrity of PSCs is maintained by a high level of transcription for a number of genes involved in DNA repair, cell cycle and apoptosis. However, it remains unclear how high the frequency of genetic mutation is and how these DNA repair factors function in PSCs. In this study, we employed Sup F assay for the measurement of mutation frequency after UV-C irradiation in induced pluripotent stem cells (iPSCs) as PSC models and neural progenitor cells (NPCs) were derived from iPSCs as differentiated cells. iPSCs and NPCs exhibited a lower mutation frequency compared with the original skin fibroblasts. In RNA-seq analysis, iPSCs and NPCs showed a high expression of RAD18, which is involved in trans-lesion synthesis (TLS) for the emergency tolerance system during the replication process of DNA. Although RAD18 is involved in both error free and error prone TLS in somatic cells, it still remains unknown the function of RAD18 in PSCs. In this study we depleted of the RAD18 by siRNA knockdown resulted in decreased frequency of mutation in iPSCs and NPCs. Our results will provide information on the genome maintenance machinery in PSCs.

Evaluating the impact of ocular UV exposure for the development for pseudoexfoliation syndrome in a South Indian population.

CLINICAL RELEVANCE: Pathophysiology of pseudoexfoliation syndrome (XFS) can be influenced by environmental factors such as solar exposure/occupational factors and genetic factors. BACKGROUND: The study aims to assess the association of lifetime ocular UV exposure and its impact on the risk of development of XFS. METHODS: All eligible subjects underwent a comprehensive ocular examination. XFS was defined as precipitates on the pupillary border, cornea, and angle of anterior chamber or lens in at least one eye without any clinical signs of glaucoma. A standardised questionnaire was administered to assess the lifetime UV exposure. Conjunctival ultraviolet autofluorescence (CUVAF) photography was taken to detect the conjunctival changes with exposure to UV radiation. Ascorbic acid concentration in the aqueous humour was measured. RESULTS: A total of 404 subjects of which 274 (controls) and 130 (XFS cases) were studied. There were 204 males (50.5%) and 200 females (49.5%).Lifetime UV exposure (OR: 1.14, 95% CI: 1.02-1.30, p: 0.032), CUVAF damage (OR: 1.03, 95% CI: 1.01-1.06, p: 0.008) and outdoor worker (OR: 1.87, 95% CI: 1.18-3.00, p: 0.008) were positively associated with XFS. Usage of spectacles (OR: 0.63, 95% CI: 0.39-0.95, p: 0.030) and ascorbic acid concentration in aqueous (OR: 0.47, 95% CI: 0.23-0.99, p: 0.038) were found to be protective against XFS. CONCLUSION: Besides genetic factors, environmental factors such as lifetime ocular UV exposure and outdoor work are significantly associated with the risk of XFS. CUVAF can be used as a non-invasive tool to detect preclinical sun damage in outdoor workers.

A Customizable and Low-Cost Ultraviolet Exposure System for Photolithography.

For microfluidic device fabrication in the research, industry, and commercial areas, the curing and transfer of patterns on photoresist relies on ultraviolet (UV) light. Often, this step is performed by commercial mask aligner or UV lamp exposure systems; however, these machines are often expensive, large, and inaccessible. To find an alternative solution, we present an inexpensive, customizable, and lightweight UV exposure system that is user-friendly and readily available for a homemade cleanroom. We fabricated a portable UV exposure system that costs under $200. The wafer holder's adjustable height enabled for the selection of the appropriate curing distance, demonstrating our system's ability to be easily tailored for different applications. The high light uniformity across a 4" diameter wafer holder (light intensity error ~2.9%) was achieved by adding a light diffusing film to the apparatus. These values are comparable to the light uniformity across a 5" diameter wafer holder from a commercial mask aligner (ABM 3000HR Mask Aligner), that has a light intensity error of ~4.0%. We demonstrated the ability to perform photolithography with high quality by fabricating microfluidic devices and generating uniform microdroplets. We achieved comparable quality to the wafer patterns, microfluidic devices, and droplets made from the ABM 3000HR Mask Aligner.

Managing the efficiencies of three different bacterial isolates for removing atrazine from wastewater.

Three individual bacterial isolates previously isolated from two types of soil with a different history of atrazine applications were chosen, purified, and subjected to subsequent work. Identification of the individual bacterial isolates was conducted using molecular methods 16S rRNA and then tested for their atrazine degradation potentials. Effects of different parameters like mixing, starvation, UV exposure, and sodium citrate for enhancing the atrazine bioremediation process by identified bacteria were also studied. The molecular method identified individual bacterial isolates as Stenotrophomonas sp. strain SD2 (strain SD2), Bacillus cereus strain BC3 (strain BC3), and Paenarthrobacter ureafaciens strain AD3 (strain AD3). The bacterial isolate strain AD3 was able to degrade 47.95% of atrazine after 28 days. Mixing strain AD3 with strain BC3 showed almost doubled of atrazine degradation percentage (61.39%) of using strain BC3 as an individual isolate (36.59%). The atrazine degradation efficacy for Stenotrophomonas sp. strain SD2, Bacillus cereus strain BC3, and Paenarthrobacter ureafaciens strain AD3 was increased between 1.28 and 4.32 folds after the starvation process. The UV exposure enhanced the efficiencies of the tested isolates either individual or mixtures (from 1.08 to 4.63-fold). Adding sodium citrate as a stimulator to the media of growing the tested isolates enhanced their potential for atrazine degradation.

The Canadian Environmental Quality Index (Can-EQI): Development and calculation of an index to assess spatial variation of environmental quality in Canada's 30 largest cities.

BACKGROUND: Multiple characteristics of the urban environment have been shown to influence population health and health-related behaviours, though the distribution and combined effects of these characteristics on health is less understood. A composite measure of multiple environmental conditions would allow for comparisons among different urban areas; however, this measure is not available in Canada. OBJECTIVES: To develop an index of environmental quality for Canada's largest urban areas and to assess the influence of population size on index values. METHODS: We conducted a systematic search of potential datasets and consulted with experts to refine and select datasets for inclusion. We identified and selected nine datasets across five domains (outdoor air pollution, natural environments, built environments, radiation, and climate/weather). Datasets were chosen based on known impacts on human health across the life course, complete geographic coverage of the cities of interest, and temporal alignment with the 2016 Canadian census. Each dataset was then summarized into dissemination areas (DAs). The Canadian Environmental Quality Index (Can-EQI) was created by summing decile ranks of each variable based on hypothesized relationships to health outcomes. RESULTS: We selected 30 cities with a population of more than 100,000 people which included 28,026 DAs and captured approximately 55% of the total Canadian population. Can-EQI scores ranged from 21.1 to 88.9 out of 100, and in Canada's largest cities were 10.2 (95% CI: -10.7, -9.7) points lower than the smallest cities. Mapping the Can-EQI revealed high geographic variability within and between cities. DISCUSSION: Our work demonstrates a valuable methodology for exploring variations in environmental conditions in Canada's largest urban areas and provides a means for exploring the role of environmental factors in explaining urban health inequalities and disparities. Additionally, the Can-EQI may be of value to municipal planners and decision makers considering the allocation of investments to improve urban conditions.

UV-Induced Somatic Mutations Driving Clonal Evolution in Healthy Skin, Nevus, and Cutaneous Melanoma.

INTRODUCTION: Due to its aggressiveness, cutaneous melanoma (CM) is responsible for most skin cancer-related deaths worldwide. The origin of CM is closely linked to the appearance of UV-induced somatic mutations in melanocytes present in normal skin or in CM precursor lesions (nevi or dysplastic nevi). In recent years, new NGS studies performed on CM tissue have increased the understanding of the genetic somatic changes underlying melanomagenesis and CM tumor progression. METHODS: We reviewed the literature using all important scientific databases. All articles related to genomic mutations in CM as well as normal skin and nevi were included, in particular those related to somatic mutations produced by UV radiation. CONCLUSIONS: CM development and progression are strongly associated with exposure to UV radiation, although each melanoma subtype has different characteristic genetic alterations and evolutionary trajectories. While BRAF and NRAS mutations are common in the early stages of tumor development for most CM subtypes, changes in CDKN2A, TP53 and PTEN, together with TERT promoter mutations, are especially common in advanced stages. Additionally, large genome duplications, loss of heterozygosity, and copy number variations are hallmarks of metastatic disease. Finally, the mutations driving melanoma targeted-therapy drug resistance are also summarized. The complete sequential stages of clonal evolution leading to CM onset from normal skin or nevi are still unknown, so further studies are needed in this field to shed light on the molecular pathways involved in CM malignant transformation and in melanoma acquired drug resistance.